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Blood neurofilament light to distinguish behavioural variant frontotemporal dementia from psychiatric conditions, and our new interactive NfL reference range app!

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We’re very pleased to share our latest publication, “Plasma neurofilament light in behavioural variant frontotemporal dementia compared to mood and psychotic disorders”, led by Dr Dhamidhu Eratne, published in Australian and New Zealand Journal of Psychiatry.

In this study, we investigated blood neurofilament light (NfL) in behavioural variant frontotemporal dementia (bvFTD) & psychiatric conditions, which can have overlapping presentations, are frequently challenging in clinical practice, with uncertainty and misdiagnosis common and associated with signifiant negative impacts for patients and their families. 

Our study had 3 main findings, all of build our goals to lead to routinely available simple blood and other tests to improve diagnosis and care for people with cognitive, neurological and psychiatric symptoms and conditions.

1) we found much higher NfL levels in bvFTD compared to mood & psychotic disorders. NfL distinguished bvFTD from psychiatric disorders with high accuracy, supporting NfL use to help with this challenging distinction in clinic

2) models using a large reference cohort allowed more precise interpretation & visualisation of an individual’s plasma NfL level. We’ve developed an interactive app to aid further research, e.g. on how such an app could be helpful in real world clinics! Please check out the app (for academic and research use only), and we’d love to hear your feedback and suggestions!

3) we found higher levels in people with bipolar disorder, compared to controls. This intriguing finding sheds more light on psychiatric conditions, could suggest some degree of neuronal injury in bipolar, & we plan on investigating this further

Thanks as always to all our incredible team of collaborators, & especially all participants, their families, & their clinicians.

Please click here to visit the journal page, or get in touch with us if you’d like a copy of the paper. Here is the abstract:

Abstract

Objective:

Blood biomarkers of neuronal injury such as neurofilament light (NfL) show promise to improve diagnosis of neurodegenerative disorders and distinguish neurodegenerative from primary psychiatric disorders (PPD). This study investigated the diagnostic utility of plasma NfL to differentiate behavioural variant frontotemporal dementia (bvFTD, a neurodegenerative disorder commonly misdiagnosed initially as PPD), from PPD, and performance of large normative/reference data sets and models.

Methods:

Plasma NfL was analysed in major depressive disorder (MDD, n = 42), bipolar affective disorder (BPAD, n = 121), treatment-resistant schizophrenia (TRS, n = 82), bvFTD (n = 22), and compared to the reference cohort (Control Group 2, n = 1926, using GAMLSS modelling), and age-matched controls (Control Group 1, n = 96, using general linear models).

Results:

Large differences were seen between bvFTD (mean NfL 34.9 pg/mL) and all PPDs and controls (all < 11 pg/mL). NfL distinguished bvFTD from PPD with high accuracy, sensitivity (86%), and specificity (88%). GAMLSS models using reference Control Group 2 facilitated precision interpretation of individual levels, while performing equally to or outperforming models using local controls. Slightly higher NfL levels were found in BPAD, compared to controls and TRS.

Conclusions:

This study adds further evidence on the diagnostic utility of NfL to distinguish bvFTD from PPD of high clinical relevance to a bvFTD differential diagnosis, and includes the largest cohort of BPAD to date. Using large reference cohorts, GAMLSS modelling and the interactive Internet-based application we developed, may have important implications for future research and clinical translation. Studies are underway investigating utility of plasma NfL in diverse neurodegenerative and primary psychiatric conditions in real-world clinical settings.